Beijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering , Peking University , Beijing 100871 , P. R. China.
Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics , Chinese Academy of Sciences , Suzhou 215123 , P. R. China.
ACS Appl Mater Interfaces. 2019 Apr 17;11(15):13973-13983. doi: 10.1021/acsami.9b01406. Epub 2019 Apr 2.
Tumor-derived extracellular vesicles (EVs) present in bodily fluids are emerging liquid biopsy markers for non-invasive cancer diagnosis and treatment monitoring. Because the majority of EVs in circulation are not of tumor origin, it is critical to develop new platforms capable of enriching tumor-derived EVs from the blood. Herein, we introduce a biostructure-inspired NanoVilli Chip, capable of highly efficient and reproducible immunoaffinity capture of tumor-derived EVs from blood plasma samples. Anti-EpCAM-grafted silicon nanowire arrays were engineered to mimic the distinctive structures of intestinal microvilli, dramatically increasing surface area and enhancing tumor-derived EV capture. RNA in the captured EVs can be recovered for downstream molecular analyses by reverse transcription Droplet Digital PCR. We demonstrate that this assay can be applied to monitor the dynamic changes of ROS1 rearrangements and epidermal growth factor receptor T790M mutations that predict treatment responses and disease progression in non-small cell lung cancer patients.
体液中存在的肿瘤衍生细胞外囊泡 (EVs) 正在成为用于非侵入性癌症诊断和治疗监测的液体活检标志物。由于循环中的大多数 EVs 并非源自肿瘤，因此开发能够从血液中富集肿瘤衍生 EVs 的新平台至关重要。在此，我们介绍了一种受生物结构启发的 NanoVilli 芯片，能够从血浆样本中高效且可重复地进行免疫亲和捕获肿瘤衍生的 EVs。抗-EpCAM 接枝硅纳米线阵列被设计用来模拟肠道微绒毛的独特结构，从而极大地增加了表面积并增强了肿瘤衍生 EV 的捕获。通过逆转录液滴数字 PCR 可以从捕获的 EV 中回收 RNA 进行下游分子分析。我们证明，该检测方法可用于监测非小细胞肺癌患者中预测治疗反应和疾病进展的 ROS1 重排和表皮生长因子受体 T790M 突变的动态变化。
